Mutant glycoproteins

Abstract

The inventors have designed novel FSH mutants with increased glycosylation and longer half-lives for use in inducing folliculogenesis in human patients. The use of a FSH mutant preparation of the invention permits the use of lower cumulative doses of FSH to achieve the same or better clinical result.

1. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH alpha subunit by the mutation F17T. 
     
     
       2. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH alpha subunit by the mutation E56N. 
     
     
       3. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH beta subunit by the mutation A70N. 
     
     
       4. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH beta subunit by the mutation V78N. 
     
     
       5. An isolated mutant of human Follicle Stimulating Hormone (FSH) having FSH activity, wherein one N-glycosylation site has been introduced into the FSH beta subunit by the mutation G100N. 
     
     
       6. An isolated mutant of human Follicle Stimulating Hormone (FSH) mutant having FSH activity, wherein one N-glycosylation site has been introduced into the FSH beta subunit by the mutations D41N/A43T. 
     
     
       7. A composition comprising the FSH mutant according to any one of  claims 1 - 6  and at least one pharmaceutically acceptable carrier or excipient. 
     
     
       8. A method of treating an infertile human, comprising administering to the human in need thereof an effective amount of the human FSH mutant according to any one of  claims 1 - 6 . 
     
     
       9. A method of stimulating folliculogenesis in a human, comprising administering to the human an effective amount of the FSH mutant according to any one of  claims 1 - 6 . 
     
     
       10. A method of inducing ovarian hyperstimulation in a human, comprising administering to the human an effective amount of the FSH mutant according to any one of  claims 1 - 6 . 
     
     
       11. An isolated nucleic acid encoding the FSH mutant of  claim 1 . 
     
     
       12. An isolated nucleic acid encoding the FSH mutant of  claim 2 . 
     
     
       13. An isolated nucleic acid encoding the FSH mutant of  claim 3 . 
     
     
       14. An isolated nucleic acid encoding the FSH mutant of  claim 4 . 
     
     
       15. An isolated nucleic acid encoding the FSH mutant of  claim 5 . 
     
     
       16. An isolated nucleic acid encoding the FSH mutant of  claim 6 . 
     
     
       17. An expression vector comprising the nucleic acid according to any one of  claims 11 - 16 . 
     
     
       18. An isolated host cell transformed with a vector according to  claim 17 . 
     
     
       19. The isolated host cell of  claim 18  which is eukaryotic. 
     
     
       20. The isolated host cell of  claim 19  which is mammalian. 
     
     
       21. A method for producing a FSH mutant, comprising subjecting the isolated host cell according to  claim 18  to cultivation under conditions conducive for expression of the FSH mutant to thereby produce the FSH mutant. 
     
     
       22. A method for producing a FSH mutant, comprising subjecting the isolated host cell according to  claim 19  to cultivation under conditions conducive for expression of the FSH mutant to thereby produce the FSH mutant. 
     
     
       23. A method for producing a FSH mutant, comprising subjecting the isolated host cell according to  claim 20  to cultivation under conditions conducive for expression of the FSH mutant to thereby produce the FSH mutant.